Treatment outcomes for rheumatoid arthritis associated interstitial lung disease; a real-world, multisite study of the impact of immunosuppression on pulmonary function trajectory

Abstract

Background Rheumatoid arthritis (RA) associated interstitial lung disease (ILD) is common in patients with RA and leads to significant morbidity and mortality. There are no randomized, placebo-controlled data to support the role of immunosuppression to treat RA-ILD despite being widely used in clinical practice. Research Question How does immunosuppression impact pulmonary function trajectory in a multi-site retrospective cohort of RA-ILD patients? Study Design and Methods Patients with RA who started treatment for ILD with mycophenolate, azathioprine, or rituximab were retrospectively identified from five ILD centers. Change in lung function before and after treatment was analyzed using a linear spline mixed effect model with random intercept. Prespecified secondary analyses examined the impact of radiologic pattern of ILD (i.e., usual interstitial pneumonia [UIP] vs non-UIP) on treatment trajectory. Results 212 patients were included in the analysis: 92 (43.4%) were treated with azathioprine, 77 (36.3%) with mycophenolate mofetil and 43 (20.3%) with rituximab. In the combined analysis of all three agents, there was an improvement in forced vital capacity (FVC) % predicted after 12 months of treatment compared to the potential 12-month response without treatment [+3.90%, p=< 0.001; 95% CI, (1.95, 5.84)]. Diffusing capacity for carbon monoxide (DLCO) % predicted also improved at 12 months [+4.53%, p=<0.001; (2.12, 6.94)]. Neither the UIP pattern of ILD or choice of immunosuppressive agent significantly impacted the pulmonary function trajectory on immunosuppression. Interpretation Immunosuppression was associated with an improved trajectory in FVC and DLCO compared to the pre-treatment pulmonary function trajectory. Prospective, randomized trials are required to validate these findings.